An Orally Defect-Rich MoO_3-x Nanozyme Enhances ROS Scavenging for Inflammatory Bowel Disease Therapy

Inflammatory bowel disease (IBD), a gastrointestinal inflammatory ailment, presents substantial therapeutic hurdles. These challenges primarily arise from the excessive generation of reactive oxygen species (ROS) and the lack of targeted treatment strategies. To address this, ultrasmall and defect-rich MoO_3-x nanozymes were fabricated through a simple liquid-phase synthesis method for boosting ROS scavenging in the treatment of inflammatory bowel disease. More specifically, the as-prepared MoO_3-x nanozymes with multivalent states and oxygen vacancies not only curtail the levels of proinflammatory cytokines and showcase notable antibacterial effects but also display catalase- and superoxide dismutase-like activities, along with hydroxyl radical scavenging properties, making them more efficient in scavenging ROS than noncatalytic antioxidants. Moreover, the greater the amount of ligands, the more excellent the nanoenzyme activity. The optimized MoO_3-x (-200) nanozymes exhibited stability in the gastric environment, making them suitable for oral delivery. In a murine model of IBD, these nanozymes alleviated colonic inflammation by reducing the levels of proinflammatory factors and myeloperoxidase (MPO) activity in colon tissues. Importantly, no significant systemic exposure was observed throughout the treatment. Furthermore, 16S rRNA sequencing analysis revealed that MoO_3-x (-200) nanozyme intervention partially modulated the composition of gut microbiota in mice with colitis, specifically promoting the augmentation of advantageous bacterial communities. This study offers novel perspectives regarding the advancement of highly effective oral formulations for the treatment of inflammatory diseases.